Military exposures and Gulf War illness in veterans with and without posttraumatic stress disorder.

Gulf War illness (GWI) is a chronic multisymptom disorder of unknown etiology that is believed to be caused by neurotoxicant exposure experienced during deployment to the Gulf War. Posttraumatic stress disorder (PTSD) covaries with GWI and is believed to play a role in GWI symptoms. The present study examined the association between self-reported military exposures and GWI, stratified by PTSD status, in veterans from the Gulf War Era Cohort and Biorepository who were deployed to the Persian Gulf during the war. Participants self-reported current GWI and PTSD symptoms as well as military exposures (e.g., pyridostigmine [PB] pills, pesticides/insecticides, combat, chemical attacks, and oil well fires) experienced during the Gulf War. Deployed veterans' (N = 921) GWI status was ascertained using the Centers for Disease Control and Prevention definition. Individuals who met the GWI criteria were stratified by PTSD status, yielding three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression, adjusted for covariates, was used to examine associations between GWI/PTSD groups and military exposures. Apart from insect bait use, the GWI+/PTSD+ group had higher odds of reporting military exposures than the GWI+/PTSD- group, adjusted odds ratio (aOR) = 2.15, 95% CI [1.30, 3.56]-aOR = 6.91, 95% CI [3.39, 14.08]. Except for PB pills, the GWI+/PTSD- group had a higher likelihood of reporting military exposures than the GWI- group, aOR = 2.03, 95% CI [1.26, 3.26]-aOR = 4.01, 95% CI [1.57, 10.25]. These findings are consistent with roles for both PTSD and military exposures in the etiology of GWI.

Bleeding outcomes of inpatients receiving therapeutic plasma exchange: A propensity-matched analysis of the National Inpatient Sample.

BACKGROUND: Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE. STUDY DESIGN AND METHODS: In a cross-sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE-treated conditions. A 1:3 propensity-matched analysis of TPE- to non-TPE-treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes. RESULTS: The study population was 15,964 discharges, of which 3991 were TPE- treated. The prevalence of major bleeding was low (5.4%). When compared to non-TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16-1.63, p = .0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42-1.94, p < .0001), in-hospital mortality (OR = 1.45, 95% CI: 1.10-1.90, p = .0008), hospital length of stay (12.45 [95% CI: 11.95-12.97] vs. 7.38 [95% CI: 7.12-7.65] days, p < .0001) and total charges, ($125,123 [95% CI: $119,220-$131,317] vs. $61,953 [95% CI: $59,391-$64,625], p < .0001), and disposition to non-self-care (OR = 1.29, 95% CI: 1.19-1.39, p < .0001). DISCUSSION: The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE-associated bleeding.

Central venous catheters are associated with thrombosis among adult inpatients undergoing therapeutic plasma exchange.

BACKGROUND: For inpatients undergoing therapeutic plasma exchange (TPE) in the United States, the primary mode of venous access is the central venous catheter (CVC). To evaluate the impact of CVC on thrombosis outcomes of patients undergoing TPE, we analyzed the National Inpatient Sample (NIS) database. STUDY DESIGN AND METHODS: In a cross-sectional analysis of the NIS, we identified hospital discharges of adult patients treated with TPE. Cases were classified into two groups based on CVC status. The primary outcome was thrombosis. Secondary outcomes were major bleeding, packed red blood cell (PRBC) transfusion, in-hospital mortality, hospital length of stay (LOS), and charges. RESULTS: Among 9863 TPE-treated discharges, CVC was used in 5988 (60%). These numbers correspond to weighted national estimates of 49 315 and 29 940, respectively. There was a positive and significant association between CVC and thrombosis (OR = 1.23, 95% 1.04-1.46, P = 0.0174), PRBC transfusion (OR = 1.15, 95% 1.03-1.29, P = 0.0121), in-hospital mortality (OR = 1.36, 95% 1.10-1.68, P = 0.0043), hospital LOS (15.63 vs 12.45 days, P < 0.0001) and hospital charges ($166 387 vs. $132 655, P < 0.0001). CONCLUSION: In hospitalized patients undergoing TPE, CVC use is associated with increased rates of thrombosis. Future studies are needed to investigate strategies to decrease CVC use and/or prevent CVC-associated complications in TPE-treated inpatients.

Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

Use of therapeutic plasma exchange in heparin-induced thrombocytopenia: A population-based study.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is characterized by anti-heparin/platelet factor 4 immune complexes, which are removed by therapeutic plasma exchange (TPE). Our main objective was to study TPE outcomes in HIT using a large administrative claims database. STUDY DESIGN AND METHODS: We used the National Inpatient Sample (NIS) to identify hospital discharges of adult patients (≥18) with a primary or secondary diagnosis of HIT. Cases were classified into two groups based on TPE use. The primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, hospital length of stay (LOS), and charges. Multivariable regression analysis, controlling for age and medical comorbidities, was used to examine the association of TPE with study outcomes. RESULTS: A HIT diagnosis was made in 22 165 discharges, of which 90 (0.4%) received TPE. Corresponding national estimates are 106 435 and 439, respectively. TPE was not associated with decreased in-hospital mortality (OR = 1.72; 95%CI: 0.93-3.17, P = .085). However, TPE was associated with a higher likelihood of major bleeding (OR = 2.35; 95%CI: 1.40-3.68, P = .0009), primarily driven by gastrointestinal bleeding (OR = 2.21; 95%CI: 1.17-4.17, P = .015). TPE was also associated with higher hospital LOS (20.5 vs 10 day, P < .0001) and charges (USD 211181 vs USD 81654, P < .0001). CONCLUSION: TPE's association with increased bleeding and a prolonged hospital course indicates that it is being used in HIT cases with a severe clinical phenotype. Future studies are needed to better characterize the HIT phenotype that will most benefit from TPE.

The Effects of Tryptophan Enhancement and Depletion on Plasma Catecholamine Levels in Healthy Individuals.

OBJECTIVE: Central nervous system (CNS) serotonin (5-HT) exerts both excitatory and inhibitory effects on the sympathetic nervous system (SNS) in animals. In this study, we examine the effects of tryptophan enhancement and depletion on plasma catecholamine levels in humans. METHODS: The total sample consisted of 164 healthy men and women who were tested for 2 days. Seventy-nine participants were randomized to a tryptophan enhancement condition and 85 to a tryptophan depletion condition. Both protocols consisted of a "sham day," followed by an "active day." Blood samples for assessment of plasma norepinephrine and epinephrine levels were collected before and after tryptophan enhancement/depletion. Data were analyzed using general linear models. Separate analyses were conducted for each study arm and for each measure. RESULTS: In the depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and norepinephrine (F(5,335) = 2.79, p = .018) showed small increases on active versus "sham" depletion days. There were also significant day by time interactions for epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked increase in epinephrine (Premean = 23.92 (12.23) versus Postmean = 81.57 (62.36)) and decrease in norepinephrine (Premean = 257.2 (106.11) versus Postmean = 177.04 (87.15)), whereas levels of both catecholamines were stable on the "sham day." CONCLUSIONS: CNS 5-HT exerts both inhibitory and excitatory effects on SNS activity in humans, potentially due to stimulation of CNS 5-HT receptors that have shown to have inhibitory (5-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS effects in animal models.

Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS: Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS: Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation , 43.33% (n=117) met criteria for MSIMI and 18.15% (n=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10µM (6.95[5.54] vs. -14.23[8.75].; P=0.045), epinephrine 10µM (12.84[4.84] vs. -6.40[7.61].; P=0.037) and to serotonin 10 µM plus ADP 1 µM (6.64[5.29] vs. -27.34[8.34]; P<.001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS: These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD.

Inflammation Markers and Major Depressive Disorder in Patients With Chronic Heart Failure: Results From the Sertraline Against Depression and Heart Disease in Chronic Heart Failure Study.

BACKGROUND: Major depressive disorder (MDD) and chronic heart failure (CHF) have in common heightening states of inflammation, manifested by elevated inflammation markers such as C-reactive protein. This study compared inflammatory biomarker profiles in patients with CHF and MDD to those without MDD. METHODS: The study recruited patients admitted to inpatient care for acute heart failure exacerbations, after psychiatric diagnostic interview. Patients with Beck Depression Inventory (BDI) scores lower than 10 and with no history of depression served as the nondepressed reference group (n = 25). MDD severity was defined as follows: mild (BDI 10-15; n = 48), moderate (BDI 16-23; n = 51), and severe (BDI ≥ 24; n = 33). A Bio-Plex assay measured 18 inflammation markers. Ordinal logistic models were used to examine the association of MDD severity and biomarker levels. RESULTS: Adjusting for age, sex, statin use, body mass index, left ventricular ejection fraction, tobacco use, and New York Heart Association class, the MDD overall group variable was significantly associated with elevated interleukin (IL)-2 (p = .019), IL-4 (p = .020), IL-6 (p = .026), interferon-γ (p = .010), monocyte chemoattractant protein 1 (p = .002), macrophage inflammatory protein 1ß (p = .003), and tumor necrosis factor α (p = .004). MDD severity subgroups had a greater probability of elevated IL-6, IL-8, interferon-γ, monocyte chemoattractant protein 1, macrophage inflammatory protein 1ß, and tumor necrosis factor α compared with nondepressed group. The nondepressed group had greater probability of elevated IL-17 (p < .001) and IL-1ß (p < .01). CONCLUSIONS: MDD in patients with CHF was associated with altered inflammation marker levels compared with patients with CHF who had no depression. Whether effective depression treatment will normalize the altered inflammation marker levels requires further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00078286.

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

BACKGROUND: Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits. PURPOSE: The purpose of this study is to determine whether central nervous system serotonin influences the association between hostility and fasting glucose in African American women. METHODS: The study consisted of 119 healthy volunteers (36 African American women, 27 White women, 21 White males, and 35 African American males, mean age 34 ± 8.5 years). Serotonin related compounds were measured in cerebrospinal fluid. Hostility was measured by the Cook-Medley Hostility Scale. RESULTS: Hostility was associated with fasting glucose and central nervous system serotonin related compounds in African American women only. Controlling for the serotonin related compounds significantly reduced the association of hostility to glucose. CONCLUSIONS: The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

Longitudinal Patterns of Multimorbidity in Gulf War Era Veterans With and Without Gulf War Illness.

Objectives: To examine whether severe Gulf War illness (SGWI) case status was associated with longitudinal multimorbidity patterns. Methods: Participants were users of the Veteran Health Administration Health Care System drawn from the Gulf War Era Cohort and Biorepository (n = 840). Longitudinal measures of multimorbidity were constructed using (1) electronic health records (Charlson Comorbidity Index; Elixhauser; and Veterans Affairs Frailty Index) from 10/1/1999 to 6/30/2023 and (2) self-reported medical conditions (Deficit Accumulation Index) since the war until the survey date. Accelerated failure time models examined SGWI case status as a predictor of time until threshold level of multimorbidity was reached, adjusted for age and sociodemographic and military characteristics. Results: Models, adjusted for covariates, revealed that (1) relative to the SWGI- group, the SGWI+ group was associated with an accelerated time for reaching each threshold and (2) the relationship between SGWI and each threshold was not moderated by age. Discussion: Findings suggest that veterans with SGWI experienced accelerated aging.

Irritable Bowel Syndrome in Veterans with Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

INTRODUCTION: Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. MATERIALS AND METHODS: We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. RESULTS: Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). CONCLUSIONS: More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease.

OBJECTIVES: The aim of this study was to examine the associations between depressive symptoms and mental stress-induced myocardial ischemia (MSIMI) in patients with coronary heart disease (CHD). METHODS: Adult patients with documented CHD were recruited for baseline mental stress and exercise stress screening testing as a part of the enrollment process of the Responses of Myocardial Ischemia to Escitalopram Treatment trial. Patients were administered the Beck Depression Inventory II and the Center for Epidemiologic Studies Depression Scale. After a 24-48-hour ß-blocker withdrawal, participants completed three mental stress tests followed by a treadmill exercise test. Ischemia was defined as a) any development or worsening of any wall motion abnormality and b) reduction of left ventricular ejection fraction at least 8% by transthoracic echocardiography and/or ischemic ST-segment change by electrocardiography during stress testing. MSIMI was considered present when ischemia occurred in at least one mental test. Data were analyzed using logistic regression adjusting for age, sex, and resting left ventricular ejection fraction. RESULTS: One hundred twenty-five (44.2%) of 283 patients were found to have MSIMI, and 93 (32.9%) had ESIMI. Unadjusted analysis showed that Beck Depression Inventory II scores were positively associated with the probability of MSIMI (odds ratio = 0.1.30: 95% confidence interval = 1.06-1.60, p = .013) and number of MSIMI-positive tasks (all p < .005). These associations were still significant after adjustment for covariates (p values <.05). CONCLUSIONS: In patients with CHD, depressive symptoms were associated with a higher probability of MSIMI. These observations may enhance our understanding of the mechanisms contributing to the association of depressive symptoms to future cardiovascular events. Trial Registration Clinicaltrials.gov identifier: NCT00574847.

Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial.

IMPORTANCE: Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied. OBJECTIVE: To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. DESIGN, SETTING, AND PARTICIPANTS: The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center. INTERVENTIONS: Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks. MAIN OUTCOMES AND MEASURES: Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks. RESULTS: Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56). CONCLUSIONS AND RELEVANCE: Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00574847.

In patients with suspected immune TTP, admission source impacts hospital length of stay and time to therapeutic plasma exchange impacts clinical outcomes.

INTRODUCTION: When immune thrombotic thrombocytopenic purpura (TTP) is suspected, outcomes are impacted by time to therapeutic plasma exchange (TPE). We evaluated the impact of time to TPE on outcomes in suspected TTP cases admitted through the Emergency Department (ED) vs. transferred from another facility (Transfer). MATERIALS AND METHODS: In a retrospective analysis of the National Inpatient Sample, we examined the association between TTP outcomes and admission source (ED vs. Transfer) for the primary outcome of time to TPE. A second stratified analyses within each analytic group examined the association of time to TPE (<1 day, 1 day, 2 days, and >2 days) and outcomes for the composite outcome of mortality, major bleeding and thrombosis. RESULTS: Of 1195 cases, 793 (66 %) were admitted through the ED and 402 (34 %) were transferred. Compared to ED cases, Transfers had a longer hospital length of stay (14.69 vs. 16.65 days, p = 0.0060). For ED cases, TPE after >2 days was associated with higher odds of the composite outcome (OR = 1.68 95 % CI: 1.11-2.54; p = 0.0150) and mortality (OR = 3.01 95 % CI: 1.38-6.57; p = 0.0056). For Transfers, TPE on day 2 was associated with higher odds of the composite outcome (OR = 3.00 95 % CI: 1.31-6.89; p = 0.0096) and mortality (OR = 4.95 95 % CI: 1.12-21.88; p = 0.0350). CONCLUSIONS: In suspected TTP admitted through the ED or transferred, there was no significant difference in time to TPE. A longer time to TPE was associated with worse outcomes. Future studies should evaluate strategies to decrease initial time to TPE.

Health-Related Quality of Life by Gulf War Illness Case Status.

This study examines how health-related quality of life (HRQOL) and related indices vary by Gulf War illness (GWI) case status. The study population included veterans from the Gulf War Era Cohort and Biorepository (n = 1116). Outcomes were physical and mental health from the Veterans RAND 12 and depression, post-traumatic stress (PTSD), sleep disturbance, and pain. Kansas (KS) and Centers for Disease Control and Prevention (CDC) GWI definitions were used. Kansas GWI derived subtypes included GWI (met symptom criteria; no exclusionary conditions (KS GWI: Sym+/Dx−)) and those without GWI: KS noncase (1): Sym+/Dx+, KS noncase (2): Sym−/Dx+, and noncase (3): Sym−/Dx−. CDC-derived subtypes included CDC GWI severe, CDC GWI mild-to-moderate and CDC noncases. Case status and outcomes were examined using multivariable regression adjusted for sociodemographic and military-related characteristics. Logistic regression analysis was used to examine associations between GWI case status and binary measures for depression, PTSD, and severe pain. The KS GWI: Sym+/Dx− and KS noncase (1): Sym+/Dx+ groups had worse mental and physical HRQOL outcomes than veterans in the KS noncase (2): Sym−/Dx+ and KS noncase (3): Sym−/Dx− groups (ps < 0.001). Individuals who met the CDC GWI severe criteria had worse mental and physical HRQOL outcomes than those meeting the CDC GWI mild-to-moderate or CDC noncases (ps < 0.001). For other outcomes, results followed a similar pattern. Relative to the less symptomatic comparison subtypes, veterans who met the Kansas symptom criteria, regardless of exclusionary conditions, and those who met the CDC GWI severe criteria experienced lower HRQOL and higher rates of depression, PTSD, and severe pain.

Association of Gulf War Illness-Related Symptoms with Military Exposures among 1990-1991 Gulf War Veterans Evaluated at the War-Related Illness and Injury Study Center (WRIISC).

Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990−1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans' reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans' severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78−9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02−5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01−5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of chronic symptoms, many of which were associated with reported neurotoxicant exposures during the war.